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This case report aims to present a case that had elevated Creatine Kinase (CK) levels during paroxetine treatment and returned to normal range after discontinuing paroxetine. This case may provide an insight with regards to paroxetine’s side effects, drug interactions, and mechanisms of action at subcellular level. The patient was 57 years old, married, unemployed female; graduated from primary school, was consulted at rheumatology outpatient unit due to CK increase 2 months after the initiation of paroxetine treatment. The patient herself began to take paroxetine 20 mg/day cope with feelings of unhappiness, lack of feelings of joy, and intense pain in August 2013. The patient had major depressive episodes in 2004 and 2008 and has used paroxetine for 6 months previously. She had no smoking, alcohol intake and substance use history. There is no connective tissue disease or psychiatric disease in her family history. An undifferentiated connective tissue disease was diagnosed in 2007 with no abnormalities in CK levels. Blood CK levels in July 2013 were observed as 714 U/l and colchicine was discontinued as decided by the department of rheumatology. However, serum CK levels remained 506 U/l in August 2013. Since then, the patient was referred to psychiatry outpatient unit and paroxetine was discontinued. After discontinuing paroxetine, CK values reduced to 311 U/l in September 2013 and then 146 U/l in the next month. In conclusion, it was considered that CK increases observed in this case were related to paroxetine. However, it is not possible to propose a causal relationship because of the present connective tissue disease and its treatment. Yet, it can be recommended that choice of paroxetine should be made carefully when an antidepressant has to be used together with medications for rheumatologic diseases.